Epidemiology of Inflammatory Bowel Diseases in Nepal.

Introduction Inflammatory bowel diseases (IBD) comprise ulcerative colitis (UC) and Crohn's disease (CD). These are diseases of the gastrointestinal tract without a clear etiology but have strong relationships with underlying factors like genetic susceptibility, environmental factors, and intestinal bacteria. In the east, inflammatory bowel diseases predominantly affect the younger population and have an almost equal gender distribution. With urbanization and the adoption of the western lifestyle, the incidence and prevalence of IBD are increasing in Asia. In this study, we describe the epidemiology of IBD in Nepal. Methods This was an observational study conducted in nine endoscopy centers within Nepal. Two years of data of colonoscopies in these centers were collected retrospectively. IBD was diagnosed by endoscopic examination. The incidence of IBD was calculated as the number of patients with IBD per 1000 colonoscopies per year. The demographic profiles of the patients were also collected. Results A total of 7526 colonoscopies were done in nine centers within the two years study period. IBD was seen in 479 patients (6.3%). The incidence of UC was 23.7 per 1000 colonoscopies per year and the incidence of CD was 1.6 per 1000 colonoscopies per year. UC (87%) was more common than CD (13%). Both UC and CD were mostly seen in the 30 to 40 years age group. In patients with UC, the rectum was the most commonly affected site. Discussion IBD in Nepal affects young males in their thirties. Younger age of affliction with a chronic disease and lack of awareness regarding the symptoms and diagnostic modalities of IBD may result in a delayed diagnosis. The target population must be made aware of the presenting symptoms of IBD and a need for colonoscopic examination for diagnosis. There is also a need for creating a national IBD registry for Nepal.

Intracolonically administered adeno-associated virus-bone morphogenetic protein-7 ameliorates dextran sulphate sodium-induced acute colitis in rats.

BACKGROUND: The current treatment of ulcerative colitis (UC) is less than ideal and has room for improvement. Bone morphogenetic protein-7 (BMP-7) exerts a protective effect on experimental UC. Hence, we considered that intracolonically (i.c.) administered adeno-associated virus (AAV) delivering BMP-7 might have therapeutic potential for UC. METHODS: Recombinant AAV type 2 vectors carrying enhanced green fluorescence protein (AAV-EGFP), LacZ (AAV-LacZ) and BMP-7 (AAV-BMP-7) were generated. Bioluminescence imaging, ß-galactosidase assay and western blotting were applied to determine the colonic expression of EGFP, LacZ and BMP-7, respectively, after i.c. administration of the AAVs. Disease activity index (DAI) was observed daily during the 7 days of dextran sulphate sodium (DSS) treatment initiated 4 days after i.c. AAV-BMP-7, AAV-LacZ or phosphate-buffered saline. The colonic pathological morphology, mucosal myeloperoxidase (MPO) activity, malondialdehyde content, superoxide dismutase activity and proliferating cell nuclear antigen were determined at the end of DSS treatment. RESULTS: When i.c administered to rats, AAV could efficiently transduce the colonic mucosa. Enema with AAV-BMP-7 significantly ameliorated DSS-induced colitis as indicated by reduced DAI, decreased macroscopic and histological scores and declined MPO activity compared to the controls. Furthermore i.c. AAV-BMP-7 significantly prevented oxidant damage and attenuated complementary mucosal cell proliferation in the DSS-treated rat colons. CONCLUSIONS: Our data demonstrate that i.c. administration of AAV-BMP-7 efficiently mediates the ectopic BMP-7 expression in rat colon and further ameliorates DSS-induced UC in rats, suggesting that i.c. AAV-BMP-7 has the potential to be developed into an alternative therapeutic measure for the treatment of UC.

Adenovirus-mediated expression of p33(ING1b) induces apoptosis and inhibits proliferation in gastric adenocarcinoma cells in vitro.

BACKGROUND: Inhibitor of growth 1b (ING1b) is considered to be a class II tumor suppressor gene. Although reduced expression of p33(ING1b) has been reported in many human malignancies, including gastric cancers, the effect of p33(ING1b) on gastric cancer cells has yet to be investigated. METHODS: Expression of p33(ING1b) in gastric adenocarcinoma tissues and their adjacent non-malignant gastric mucosa, as well as in gastric adenocarcinoma cell lines and normal gastric epithelial cells, was detected by using Western blotting. Recombinant adenoviruses were prepared to mediate the ectopic expression of p33(ING1b) (Ad-ING1b) and green fluorescent protein (GFP)(Ad-GFP) in the gastric adenocarcinoma cell lines, SGC-7901, MKN28, and MKN45 and the normal gastric epithelial cell line GES-1. Alterations in the proliferation and apoptosis of the cells after adenoviral infection were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively, and cell cycle distribution was analyzed in a fluorescence-activated cell sorter. RESULTS: Western blotting confirmed the reduced expression of p33(ING1b) in gastric adenocarcinoma tissues and gastric adenocarcinoma cell lines. The ectopic expression of p33(ING1b) mediated by Ad-ING1b resulted in decreased growth, increased apoptosis, and cell cycle arrest at the G1 phase in both benign and malignant gastric epithelial cells regardless of their p53 status. Addition of a p53 inhibitor, pifithrin-α, did not abolish the pro-apoptotic and cell cycle-arresting effects of p33(ING1b) in p53 wild-type cells. CONCLUSIONS: Down-regulation of p33(ING1b) might play an important role in the development of gastric adenocarcinoma. Targeted local expression of p33(ING1b) may offer a promising alternative therapeutic measure for gastric cancer.